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Sökning: WFRF:(Belghiti J)

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  • Thors, Lina, 1981-, et al. (författare)
  • Inhibition of fatty acid amide hydrolase by kaempferol and related naturally occurring flavonoids
  • 2008
  • Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 155:2, s. 244-252
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Recent studies have demonstrated that the naturally occurring isoflavone compounds genistein and daidzein inhibit the hydrolysis of anandamide by fatty acid amide hydrolase (FAAH) in the low micromolar concentration range. The purpose of the present study was to determine whether this property is shared by flavonoids.EXPERIMENTAL APPROACH:The hydrolysis of anandamide in homogenates and intact cells was measured using the substrate labelled in the ethanolamine part of the molecule.KEY RESULTS: Twenty compounds were tested. Among the commonly occurring flavonoids, kaempferol was the most potent, inhibiting FAAH in a competitive manner with a K(i) value of 5 microM. Among flavonoids with a more restricted distribution in nature, the two most active toward FAAH were 7-hydroxyflavone (IC(50) value of 0.5-1 microM depending on the solvent used) and 3,7-dihydroxyflavone (IC(50) value 2.2 microM). All three compounds reduced the FAAH-dependent uptake of anandamide and its metabolism by intact RBL2H3 basophilic leukaemia cells.CONCLUSIONS AND IMPLICATIONS: Inhibition of FAAH is an additional in vitro biochemical property of flavonoids. Kaempferol, 7-hydroxyflavone and 3,7-dihydroxyflavone may be useful as templates for the synthesis of novel compounds, which target several systems that are involved in the control of inflammation and cancer.
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